{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:00:01Z","timestamp":1791388801228,"version":"4.3.3"},"reference-count":10,"publisher":"Bioscientifica","license":[{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["edm.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,2,1]]},"abstract":"<jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>Immunotherapy has become an important pillar for the management of advanced cancer. Immune-related adverse events including endocrinopathies have been well described with programmed cell death 1 inhibitors such as pembrolizumab. While thyroid dysfunction is the most common endocrinopathy associated with pembrolizumab, new-onset autoimmune diabetes mellitus (DM) is extremely rare. The authors report a case of pembrolizumab-induced primary hypothyroidism and type 1 diabetes mellitus presenting with diabetic ketoacidosis (DKA). A 59-year-old female patient was treated with pembrolizumab for a stage 4 lung adenocarcinoma. She presented to the emergency department with hyperglycaemia-related signs and symptoms, such as polyuria, polydipsia, weight loss, vomiting, asthenia and dehydration, 3 weeks after her first dose of pembrolizumab. Laboratory evaluation revealed hyperglycaemia, hyperketonaemia and high anion gap metabolic acidaemia consistent with DKA. After prompt and adequate treatment of DKA, she transitioned to s.c. basal-bolus insulin. The diagnose of autoimmune DM was established based on the undetectable C-peptide levels and seropositivity for antiglutamic acid decarboxylase antibodies. Additional hormonal parameters revealed overt hypothyroidism and levothyroxine therapy was initiated. This case highlights the importance of blood glucose and thyroid function monitoring as an integral part of cancer treatment protocols for pembrolizumab and other immune checkpoint inhibitors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Learning points<\/jats:title>\n                    <jats:list list-type=\"bullet\">\n                      <jats:list-item>\n                        <jats:p>Programmed cell death 1 (PD1) inhibitors such as pembrolizumab can cause endocrine immune-related adverse events (irAE), including thyroid dysfunction and type 1 diabetes mellitus (T1DM).<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Thyroid dysfunction is the most frequent endocrine irAE secondary to PD1 inhibitors.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Autoimmune diabetes and possible resultant diabetic ketoacidosis are rare, but life-threatening adverse events associated with pembrolizumab.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Pembrolizumab-induced T1DM often present with relatively low HbAlc levels, reflecting the fulminant onset of \u03b2-cell destruction.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Patients treated with pembrolizumab and other immune checkpoints inhibitors should be monitored regularly for hyperglycaemia and thyroid dysfunction.<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:sec>","DOI":"10.1530\/edm-21-0123","type":"journal-article","created":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T04:47:15Z","timestamp":1644468435000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-2","source":"Crossref","is-referenced-by-count":6,"title":["New onset autoimmune diabetes mellitus and hypothyroidism secondary to pembrolizumab in a patient with metastatic lung cancer"],"prefix":"10.1530","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9229-2092","authenticated-orcid":true,"given":"Clara","family":"Cunha","sequence":"first","affiliation":[{"name":"Department of Endocrinology Hospital Egas Moniz, Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eug\u00e9nia","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Hospital Egas Moniz, Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Cl\u00e1udia","family":"Vieira","sequence":"additional","affiliation":[{"name":"Department of Pneumology, Hospital Egas Moniz, Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catarina","family":"Saraiva","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Hospital Egas Moniz, Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sequeira","family":"Duarte","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Hospital Egas Moniz, Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Endocrinology, Diabetes and Metabolism Case Reports","first-page":"18","article-title":"A case of pembrolizumab-induced severe DKA and hypothyroidism in a patient with metastatic melanoma","volume":"2019","author":"Hakami","year":"2019","unstructured":"Hakami OAIoana JAhmad STun TKSreenan SMcDermott JH. A case of pembrolizumab-induced severe DKA and hypothyroidism in a patient with metastatic melanoma. Endocrinology, Diabetes and Metabolism Case Reports2019201918-0153. (https:\/\/doi.org\/10.1530\/EDM-18-0153)"},{"key":"bib2","series-title":"Endocrine-Related Cancer","doi-asserted-by":"publisher","first-page":"G1","DOI":"10.1530\/ERC-18-0320","article-title":"French Endocrine Society Guidance on endocrine side effects of immunotherapy","volume":"26","author":"Castinetti","year":"2019","unstructured":"Castinetti FAlbarel FArchambeaud FBertherat JBouillet BBuffier PBriet CCariou BCaron PChabre Oet al. French Endocrine Society Guidance on endocrine side effects of immunotherapy. Endocrine-Related Cancer201926G1\u2013G18. (https:\/\/doi.org\/10.1530\/ERC-18-0320)10.1530\/ERC-18-0320"},{"key":"bib3","series-title":"Diabetes Care","doi-asserted-by":"publisher","first-page":"e137","DOI":"10.2337\/dc15-0889","article-title":"Anti-PD1 and anti-PD-L1 monoclonal antibodies causing type 1 diabetes","volume":"38","author":"Mellati","year":"2015","unstructured":"Mellati MEaton KDBrooks-Worrell BMHagopian WAMartins RPalmer JPHirsch IB. Anti-PD1 and anti-PD-L1 monoclonal antibodies causing type 1 diabetes. Diabetes Care201538e137\u2013e138. (https:\/\/doi.org\/10.2337\/dc15-0889)10.2337\/dc15-0889"},{"key":"bib4","article-title":"Pembrolizumab FDA label","unstructured":"U.S. Food and Drug Administration. Pembrolizumab FDA label. (available at reference ID:4625717). Last updated June 2020."},{"key":"bib5","series-title":"BMJ Case Reports","first-page":"bcr2017220999","article-title":"New onset diabetes after nivolumab treatment","volume":"2018","author":"Capitao","year":"2018","unstructured":"Capitao RBello CFonseca RSaraiva C. New onset diabetes after nivolumab treatment. BMJ Case Reports20182018bcr2017220999. (https:\/\/doi.org\/10.1136\/bcr-2017-220999)"},{"key":"bib6","series-title":"Cancer Immunology, Immunotherapy","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1007\/s00262-017-2033-8","article-title":"Autoimmune diabetes induced by PD-1 inhibitor-retrospective analysis and pathogenesis: a case report and literature review","volume":"66","author":"Gauci","year":"2017","unstructured":"Gauci MLLaly PVidal-Trecan TBaroudjian BGottlieb JMadjlessi-Ezra NDa Meda LMadelaine-Chambrin IBagot MBasset-Seguin Net al. Autoimmune diabetes induced by PD-1 inhibitor-retrospective analysis and pathogenesis: a case report and literature review. 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